Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer

Andrés J Muñoz Martín, Israel Ortega, Carme Font, Vanesa Pachón, Victoria Castellón, Virginia Martínez-Marín, Mercedes Salgado, Eva Martínez, Julia Calzas, Ana Rupérez, Juan C Souto, Miguel Martín, Eduardo Salas, Jose M Soria, Andrés J Muñoz Martín, Israel Ortega, Carme Font, Vanesa Pachón, Victoria Castellón, Virginia Martínez-Marín, Mercedes Salgado, Eva Martínez, Julia Calzas, Ana Rupérez, Juan C Souto, Miguel Martín, Eduardo Salas, Jose M Soria

Abstract

Background: Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. Outpatients with cancer should be periodically assessed for VTE risk, for which the Khorana score is commonly recommended. However, it has been questioned whether this tool is sufficiently accurate at identifying patients who should receive thromboprophylaxis. The present work proposes a new index, TiC-Onco risk score to be calculated at the time of diagnosis of cancer, that examines patients' clinical and genetic risk factors for thrombosis.

Methods: We included 391 outpatients with a recent diagnosis of cancer and candidates for systemic outpatient chemotherapy. All were treated according to standard guidelines. The study population was monitored for 6 months, and VTEs were recorded. The Khorana and the TiC-Onco scores were calculated for each patient and their VTE predictive accuracy VTEs was compared.

Results: We recorded 71 VTEs. The TiC-Onco risk score was significantly better at predicting VTE than the Khorana score (AUC 0.73 vs. 0.58, sensitivity 49 vs. 22%, specificity 81 vs. 82%, PPV 37 vs. 22%, and NPV 88 vs. 82%).

Conclusions: TiC-Onco risk score performed significantly better than Khorana score at identifying cancer patients at high risk of VTE who would benefit from personalised thromboprophylaxis.

Conflict of interest statement

A.M., J.M.S., and E.S. are inventors in a patent application claiming the use of TiC-Onco. A.M. and Jose M.S will receive royalties for giving the right to Gendiag of being the assignee of that patent application. Israel Ortega and Eduardo Salas are employees of Gendiag. C.F., V.P., V.C., V.M-M., M.S., E.M., J.C., A.R., M.M., and J.C.S. have no conflic of interest.

References

    1. Blom JW, Doggen CJM, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293:715–722. doi: 10.1001/jama.293.6.715.
    1. Khorana AA, Dalal M, Lin J, Connolly GC. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer. 2013;119:648–655. doi: 10.1002/cncr.27772.
    1. Noble S, Pasi J. Epidemiology and pathophysiology of cancer-associated thrombosis. Br. J. Cancer. 2010;102:S2–S9. doi: 10.1038/sj.bjc.6605599.
    1. Lyman GH, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society Of Clinical Oncology Clinical Practice Guideline Update 2014. J. Clin. Oncol. 2015;33:654–656. doi: 10.1200/JCO.2014.59.7351.
    1. Muñoz Martín AJ, Font Puig C, Navarro Martín LM, Borrega García P, Martín Jiménez M. Clinical guide SEOM on venous thromboembolism in cancer patients. Clinical Transl. Oncol. 2014;16:1079–1090. doi: 10.1007/s12094-014-1238-y.
    1. Falanga A, Roila F, Mandala M. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines clinical practice guidelines. Ann. Oncol. 22. 2011;22:85–92.
    1. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2015;111:4902–4908. doi: 10.1182/blood-2007-10-116327.
    1. Muñoz Martín AJ, et al. Incidence of venous thromboembolism (VTE) in ambulatory pancreatic cancer patients receiving chemotherapy and analysis of Khorana’s predictive model. Clinical & Transl. Oncol. 2014;16:927–930. doi: 10.1007/s12094-014-1165-y.
    1. Srikanthan A, et al. Large retroperitoneal lymphadenopathy as a predictor of venous thromboembolism in patients with disseminated germ cell tumors treated with chemotherapy. Journal. clinical Oncol. 2015;33:582–587. doi: 10.1200/JCO.2014.58.6537.
    1. Ugarte Fornell G, et al. Predictive Khorana’s model in patients with venous thromboembolic disease and cancer. Med. clínica. 2013;141:479–481. doi: 10.1016/j.medcli.2013.04.031.
    1. Pabinger I, et al. Factor V Leiden mutation increases the risk for venous thromboembolism in cancer patients-results from the Vienna Cancer And Thrombosis Study (CATS) Journal. Thromb. Haemost. 2015;13:17–22. doi: 10.1111/jth.12778.
    1. Tinholt Mari, Sandset Per Morten, Iversen Nina. Polymorphisms of the coagulation system and risk of cancer. Thrombosis Research. 2016;140:S49–S54. doi: 10.1016/S0049-3848(16)30098-6.
    1. Soria JM, et al. Multilocus genetic risk scores for venous thromboembolism risk assessment. Journal. Am. Heart Assoc. 2014;3:e001060. doi: 10.1161/JAHA.114.001060.
    1. Falanga A, Russo L. Epidemiology, risk and outcomes of venous thromboembolism in cancer. Hamostaseologie. 2012;32:115–125. doi: 10.5482/ha-1170.
    1. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902–4907. doi: 10.1182/blood-2007-10-116327.
    1. Venables W. N., Ripley B. D. Modern Applied Statistics with S. New York, NY: Springer New York; 2002.
    1. Smith GC, Seaman SR, Wood AM, Royston P, White IR. Correcting for optimistic prediction in small data sets. Am. J. Epidemiol. 2014;180:318–324. doi: 10.1093/aje/kwu140.
    1. Hanley Ja, Hajian-Tilaki KO. Sampling variability of nonparametric estimates of the areas under receiver operating characteristic curves: an update. Acad. Radiol. 1997;4:49–58. doi: 10.1016/S1076-6332(97)80161-4.
    1. Attia J. Moving beyond sensitivity and specificity: using likelihood ratios to. Aust. Prescr. 2003;26:111–113. doi: 10.18773/austprescr.2003.082.
    1. Schisterman EF, Perkins NJ, Liu A, Bondell H. Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples. Epidemiology. 2005;16:73–81. doi: 10.1097/.
    1. R Development Core Team (2015) R: a Language and Enviroment for Statistical Computing. (R Foundation for Statistical Computing, Vienna, 2015).
    1. Sackett DL, Haynes RB. Summarizing the effects of therapy: a new table and some more terms. Acp. J. Club. 1997;127:A15–A16.
    1. Di Nisio M, Porreca E, Otten HM, Rutjes AWS. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst. Rev. 2014;8:CD008500.
    1. Streiff MB, et al. Cancer-associated venous thromboembolic disease, version 1.2015. Journal. Natl. Compr. Cancer Netw. 2015;13:1079–1095. doi: 10.6004/jnccn.2015.0133.
    1. Qureshi W, et al. Venous thromboembolism in cancer: an update of treatment and prevention in the era of newer anticoagulants. Front. Cardiovasc. Med. Front. 2016;3:24.
    1. Ay C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377–5382. doi: 10.1182/blood-2010-02-270116.
    1. Thaler J, Ay C, Pabinger I. Venous thromboembolism in cancer patients- Risk scores and recent randomised controlled trials. Thromb. Haemost. 2012;108:1042–1048. doi: 10.1160/TH12-04-0241.
    1. Pihusch R, et al. Impact of thrombophilic gene mutations on thrombosis risk in patients with gastrointestinal carcinoma. Cancer. 2002;94:3120–3126. doi: 10.1002/cncr.10590.
    1. Gran OV, et al. Joint effects of cancer and variants in the factor 5 gene on the risk of venous thromboembolism. Haematologica. 2016;101:1046–1053. doi: 10.3324/haematol.2016.147405.
    1. Kennedy M, et al. Factor V Leiden, prothrombin 20210A and the risk of venous thrombosis among cancer patients. Br. J. Haematol. 2005;128:386–388. doi: 10.1111/j.1365-2141.2004.05327.x.
    1. Khorana AA, Dalal M, Lin J, Connolly GC. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer. 2013;119:648–655. doi: 10.1002/cncr.27772.
    1. Gran OV, et al. Joint effects of cancer and variants in the factor 5 gene on the risk of venous thromboembolism. Haematol. Haematol. 2016;101:1046–1053. doi: 10.3324/haematol.2016.147405.
    1. Lyman GH, Bohlke K, Falanga A, American Society of Clinical Oncology. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. Journal. Oncol. Pract. 2015;11:e442–e444. doi: 10.1200/JOP.2015.004473.

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